Trial Outcomes & Findings for Polatuzumab Vedotin, Venetoclax, and Rituximab and Hyaluronidase Human for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma (NCT NCT04659044)
NCT ID: NCT04659044
Last Updated: 2024-09-19
Results Overview
Objective status of CR measured by positron emission tomography (PET)-computed tomography (CT) scans according to Lugano 2014.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
3 participants
Primary outcome timeframe
3 months
Results posted on
2024-09-19
Participant Flow
Participant milestones
| Measure |
Treatment (Rituximab, Polatuzumab Vedotin, Venetoclax)
INDUCTION: Patients receive rituximab IV on day 1 of cycle 1 and rituximab and hyaluronidase human SC over 5 minutes on day 1 of cycles 2-6. Patients also receive polatuzumab vedotin IV over 30-90 minutes on day 1 and venetoclax PO daily on days 1-21. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive venetoclax PO daily on days 1-21 and rituximab and hyaluronidase human SC over 5 minutes every 60 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
Polatuzumab Vedotin: Given IV
Rituximab: Given IV
Rituximab and Hyaluronidase Human: Given SC
Venetoclax: Given PO
|
|---|---|
|
Induction
STARTED
|
3
|
|
Induction
COMPLETED
|
0
|
|
Induction
NOT COMPLETED
|
3
|
|
Maintenance Therapy
STARTED
|
0
|
|
Maintenance Therapy
COMPLETED
|
0
|
|
Maintenance Therapy
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
Treatment (Rituximab, Polatuzumab Vedotin, Venetoclax)
INDUCTION: Patients receive rituximab IV on day 1 of cycle 1 and rituximab and hyaluronidase human SC over 5 minutes on day 1 of cycles 2-6. Patients also receive polatuzumab vedotin IV over 30-90 minutes on day 1 and venetoclax PO daily on days 1-21. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive venetoclax PO daily on days 1-21 and rituximab and hyaluronidase human SC over 5 minutes every 60 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
Polatuzumab Vedotin: Given IV
Rituximab: Given IV
Rituximab and Hyaluronidase Human: Given SC
Venetoclax: Given PO
|
|---|---|
|
Induction
Physician Decision
|
1
|
|
Induction
Adverse Event
|
2
|
Baseline Characteristics
Polatuzumab Vedotin, Venetoclax, and Rituximab and Hyaluronidase Human for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma
Baseline characteristics by cohort
| Measure |
Treatment (Rituximab, Polatuzumab Vedotin, Venetoclax)
n=3 Participants
INDUCTION: Patients receive rituximab IV on day 1 of cycle 1 and rituximab and hyaluronidase human SC over 5 minutes on day 1 of cycles 2-6. Patients also receive polatuzumab vedotin IV over 30-90 minutes on day 1 and venetoclax PO daily on days 1-21. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive venetoclax PO daily on days 1-21 and rituximab and hyaluronidase human SC over 5 minutes every 60 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
Polatuzumab Vedotin: Given IV
Rituximab: Given IV
Rituximab and Hyaluronidase Human: Given SC
Venetoclax: Given PO
|
|---|---|
|
Age, Continuous
|
62.1 years
STANDARD_DEVIATION 19.89 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=5 Participants
|
|
ECOG Performance Status
<=1
|
2 Participants
n=5 Participants
|
|
ECOG Performance Status
>=2
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 3 monthsPopulation: Only patients that had at least one post-baseline disease assessment were included in analysis
Objective status of CR measured by positron emission tomography (PET)-computed tomography (CT) scans according to Lugano 2014.
Outcome measures
| Measure |
Treatment (Rituximab, Polatuzumab Vedotin, Venetoclax)
n=2 Participants
INDUCTION: Patients receive rituximab IV on day 1 of cycle 1 and rituximab and hyaluronidase human SC over 5 minutes on day 1 of cycles 2-6. Patients also receive polatuzumab vedotin IV over 30-90 minutes on day 1 and venetoclax PO daily on days 1-21. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive venetoclax PO daily on days 1-21 and rituximab and hyaluronidase human SC over 5 minutes every 60 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
Polatuzumab Vedotin: Given IV
Rituximab: Given IV
Rituximab and Hyaluronidase Human: Given SC
Venetoclax: Given PO
|
|---|---|
|
Number of Patients Experiencing a Complete Response (CR)
|
0 Participants
|
SECONDARY outcome
Timeframe: 3 monthsPopulation: Only patients that had at least one post-baseline disease assessment were included in analysis
The ORR at the end of induction will be estimated by the total number of patients who achieve a complete response (CR) or partial response (PR) by PET-CT scans according to Lugano 2014 divided by the total number of evaluable patients. The ORR between ibrutinib-naive and ibrutinib-pretreated patients will be compared using Fisher's exact test.
Outcome measures
| Measure |
Treatment (Rituximab, Polatuzumab Vedotin, Venetoclax)
n=2 Participants
INDUCTION: Patients receive rituximab IV on day 1 of cycle 1 and rituximab and hyaluronidase human SC over 5 minutes on day 1 of cycles 2-6. Patients also receive polatuzumab vedotin IV over 30-90 minutes on day 1 and venetoclax PO daily on days 1-21. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive venetoclax PO daily on days 1-21 and rituximab and hyaluronidase human SC over 5 minutes every 60 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
Polatuzumab Vedotin: Given IV
Rituximab: Given IV
Rituximab and Hyaluronidase Human: Given SC
Venetoclax: Given PO
|
|---|---|
|
Overall Response Rate (ORR)
|
0 Participants
|
SECONDARY outcome
Timeframe: At the end of maintenance therapyPopulation: No patients were on study long enough to receive maintenance therapy.
CR, PR, and stable disease (SD) rates for patients who continue to maintenance will be estimated by number of patients who continue on maintenance therapy and achieve CR, PR or SD, respectively, at the end of maintenance divided by the total number of evaluable patients who continue to maintenance.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 10 monthsPopulation: Only patients that had at least one post-baseline disease assessment were included in analysis
The distribution of PFS will be estimated using the method of Kaplan-Meier. The PFS between ibrutinib-naive and ibrutinib-pretreated patients will be compared using log-rank test.
Outcome measures
| Measure |
Treatment (Rituximab, Polatuzumab Vedotin, Venetoclax)
n=2 Participants
INDUCTION: Patients receive rituximab IV on day 1 of cycle 1 and rituximab and hyaluronidase human SC over 5 minutes on day 1 of cycles 2-6. Patients also receive polatuzumab vedotin IV over 30-90 minutes on day 1 and venetoclax PO daily on days 1-21. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive venetoclax PO daily on days 1-21 and rituximab and hyaluronidase human SC over 5 minutes every 60 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
Polatuzumab Vedotin: Given IV
Rituximab: Given IV
Rituximab and Hyaluronidase Human: Given SC
Venetoclax: Given PO
|
|---|---|
|
Progression Free Survival (PFS)
|
5.5 months
Interval 1.1 to
The upper limit of the confidence interval cannot be estimated due to a low number of events.
|
SECONDARY outcome
Timeframe: 15 monthsPopulation: Only patients that had at least one post-baseline disease assessment were included in analysis
The distribution of OS will be estimated using the method of Kaplan-Meier. The OS between ibrutinib-naive and ibrutinib-pretreated patients will be compared using log-rank test.
Outcome measures
| Measure |
Treatment (Rituximab, Polatuzumab Vedotin, Venetoclax)
n=2 Participants
INDUCTION: Patients receive rituximab IV on day 1 of cycle 1 and rituximab and hyaluronidase human SC over 5 minutes on day 1 of cycles 2-6. Patients also receive polatuzumab vedotin IV over 30-90 minutes on day 1 and venetoclax PO daily on days 1-21. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive venetoclax PO daily on days 1-21 and rituximab and hyaluronidase human SC over 5 minutes every 60 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
Polatuzumab Vedotin: Given IV
Rituximab: Given IV
Rituximab and Hyaluronidase Human: Given SC
Venetoclax: Given PO
|
|---|---|
|
Overall Survival (OS)
|
NA months
Interval 1.1 to
The median survival time and upper limit of the confidence interval cannot be estimated due to a low number of events.
|
SECONDARY outcome
Timeframe: 15 monthsAll AEs occurring on or after first study treatment will be summarized by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 grade.
Outcome measures
| Measure |
Treatment (Rituximab, Polatuzumab Vedotin, Venetoclax)
n=3 Participants
INDUCTION: Patients receive rituximab IV on day 1 of cycle 1 and rituximab and hyaluronidase human SC over 5 minutes on day 1 of cycles 2-6. Patients also receive polatuzumab vedotin IV over 30-90 minutes on day 1 and venetoclax PO daily on days 1-21. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive venetoclax PO daily on days 1-21 and rituximab and hyaluronidase human SC over 5 minutes every 60 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
Polatuzumab Vedotin: Given IV
Rituximab: Given IV
Rituximab and Hyaluronidase Human: Given SC
Venetoclax: Given PO
|
|---|---|
|
Count of Patients Experiencing Grade 3+ Adverse Events (AEs)
|
3 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to the end of maintenance therapyMRD status for both responders and non-responders at each time point will be reported descriptively, and explored for correlation with clinical factors and patient outcomes such as PFS and OS.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to the end of maintenance therapySystemic immune profiles and T cell activation will be investigated using multi-parameter flow cytometry, and cytokine analysis in the peripheral blood of patients.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to the end of maintenance therapyWill be summarized using frequency and percentages.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to the end of maintenance therapyWill be summarized using frequency and percentages.
Outcome measures
Outcome data not reported
Adverse Events
Treatment (Rituximab, Polatuzumab Vedotin, Venetoclax)
Serious events: 2 serious events
Other events: 3 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Treatment (Rituximab, Polatuzumab Vedotin, Venetoclax)
n=3 participants at risk
INDUCTION: Patients receive rituximab IV on day 1 of cycle 1 and rituximab and hyaluronidase human SC over 5 minutes on day 1 of cycles 2-6. Patients also receive polatuzumab vedotin IV over 30-90 minutes on day 1 and venetoclax PO daily on days 1-21. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive venetoclax PO daily on days 1-21 and rituximab and hyaluronidase human SC over 5 minutes every 60 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
Polatuzumab Vedotin: Given IV
Rituximab: Given IV
Rituximab and Hyaluronidase Human: Given SC
Venetoclax: Given PO
|
|---|---|
|
Investigations
Neutrophil count decreased
|
33.3%
1/3 • Number of events 2 • 15 months
|
|
Investigations
White blood cell decreased
|
33.3%
1/3 • Number of events 1 • 15 months
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
33.3%
1/3 • Number of events 1 • 15 months
|
|
Blood and lymphatic system disorders
Anemia
|
33.3%
1/3 • Number of events 1 • 15 months
|
|
General disorders
Disease Progression
|
33.3%
1/3 • Number of events 1 • 15 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
33.3%
1/3 • Number of events 1 • 15 months
|
|
Investigations
Platelet count decreased
|
33.3%
1/3 • Number of events 2 • 15 months
|
|
Metabolism and nutrition disorders
Tumor lysis syndrome
|
33.3%
1/3 • Number of events 1 • 15 months
|
|
Infections and infestations
Lung infection
|
33.3%
1/3 • Number of events 1 • 15 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
33.3%
1/3 • Number of events 1 • 15 months
|
Other adverse events
| Measure |
Treatment (Rituximab, Polatuzumab Vedotin, Venetoclax)
n=3 participants at risk
INDUCTION: Patients receive rituximab IV on day 1 of cycle 1 and rituximab and hyaluronidase human SC over 5 minutes on day 1 of cycles 2-6. Patients also receive polatuzumab vedotin IV over 30-90 minutes on day 1 and venetoclax PO daily on days 1-21. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive venetoclax PO daily on days 1-21 and rituximab and hyaluronidase human SC over 5 minutes every 60 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
Polatuzumab Vedotin: Given IV
Rituximab: Given IV
Rituximab and Hyaluronidase Human: Given SC
Venetoclax: Given PO
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
33.3%
1/3 • Number of events 1 • 15 months
|
|
Investigations
Alanine aminotransferase increased
|
33.3%
1/3 • Number of events 10 • 15 months
|
|
Blood and lymphatic system disorders
Anemia
|
66.7%
2/3 • Number of events 5 • 15 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
33.3%
1/3 • Number of events 1 • 15 months
|
|
Investigations
Aspartate aminotransferase increased
|
33.3%
1/3 • Number of events 8 • 15 months
|
|
Investigations
Blood lactate dehydrogenase increased
|
66.7%
2/3 • Number of events 2 • 15 months
|
|
Investigations
Cholesterol high
|
33.3%
1/3 • Number of events 1 • 15 months
|
|
Gastrointestinal disorders
Constipation
|
33.3%
1/3 • Number of events 2 • 15 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
66.7%
2/3 • Number of events 2 • 15 months
|
|
General disorders
Fatigue
|
33.3%
1/3 • Number of events 1 • 15 months
|
|
General disorders
Fever
|
33.3%
1/3 • Number of events 1 • 15 months
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
33.3%
1/3 • Number of events 1 • 15 months
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
33.3%
1/3 • Number of events 1 • 15 months
|
|
Investigations
GGT increased
|
33.3%
1/3 • Number of events 1 • 15 months
|
|
Nervous system disorders
Headache
|
33.3%
1/3 • Number of events 1 • 15 months
|
|
Metabolism and nutrition disorders
Hyperphosphatemia
|
33.3%
1/3 • Number of events 4 • 15 months
|
|
Vascular disorders
Hypotension
|
33.3%
1/3 • Number of events 1 • 15 months
|
|
Psychiatric disorders
Insomnia
|
33.3%
1/3 • Number of events 1 • 15 months
|
|
Blood and lymphatic system disorders
Lymph node pain
|
33.3%
1/3 • Number of events 1 • 15 months
|
|
Investigations
Lymphocyte count decreased
|
66.7%
2/3 • Number of events 10 • 15 months
|
|
General disorders
Malaise
|
33.3%
1/3 • Number of events 2 • 15 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
33.3%
1/3 • Number of events 2 • 15 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
33.3%
1/3 • Number of events 2 • 15 months
|
|
Gastrointestinal disorders
Nausea
|
33.3%
1/3 • Number of events 1 • 15 months
|
|
Investigations
Neutrophil count decreased
|
66.7%
2/3 • Number of events 3 • 15 months
|
|
General disorders
Pain
|
33.3%
1/3 • Number of events 3 • 15 months
|
|
Nervous system disorders
Paresthesia
|
33.3%
1/3 • Number of events 1 • 15 months
|
|
Nervous system disorders
Peripheral motor neuropathy
|
33.3%
1/3 • Number of events 1 • 15 months
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
66.7%
2/3 • Number of events 2 • 15 months
|
|
Investigations
Platelet count decreased
|
66.7%
2/3 • Number of events 3 • 15 months
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhea
|
33.3%
1/3 • Number of events 1 • 15 months
|
|
Investigations
White blood cell decreased
|
66.7%
2/3 • Number of events 7 • 15 months
|
Additional Information
Catherine Diefenbach M.D.
Perlmutter Cancer Center at NYU Langone Health
Phone: (212) 731-5670
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place